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Can Probiotics Reduce Candida
Infections?
Peter Cartwright MSc MA
Human Microbiota Specialist, Probiotics International Ltd.
Candida in the Microflora
At least one-third of healthy individuals carry the Candida
fungus; in the mouth, the intestine or the vagina1,2,3,4. This
prevalence, without symptoms, means that Candida can be
considered a member of the normal microflora of human
beings5. The microflora are communities of microscopic
organisms that live with us for the whole of our lives, and are
beneficial to our health.
Under certain circumstances, however, Candida fungus can
cause infectious disease, which occasionally can take a very
serious form. How can a microorganism be a member of our
microflora and also cause disease?
Why is Candida such a Troublesome
Opportunistic Pathogen?
As a fungus, Candida is unlike the vast majority of microbes in
the human flora, which are bacteria. A bacterium is a
prokaryote (containing no nucleus or other organelles), while
a fungus is a eukaryote, which is a more complex type of cell,
closer in evolutionary terms to a human cell. Such greater
complexity makes Candida a troublesome microbe when it
switches into pathogenic mode.
Candida albicans is the species responsible for the majority of
infections, but other species such as Candida glabrata,
Candida parapsilosis and Candida tropicalis are also
pathogenic in humans8.
The answer to this question is not yet known for certain, but
it could be that Candida provides benefits to the host and is
therefore accepted. Alternatively, Candida could be a
pathogen that is very tricky to eradicate, but is controlled by
the normal microflora. As no benefits from Candida have yet
been identified, the second explanation seems more likely.
In most people, the risk from Candida is low, because the
fungus constitutes a very small proportion of the overall
microfloral population. Several studies have found that only
about 3-4,000 Candida cells are present in 1 gram of content
of the large intestine. This is a tiny number compared with
the billions of bacteria found in the same amount of colonic
content2,3,4,6.
Despite the relatively low risk from Candida in the microflora,
and the development of new anti-fungal drugs, the incidence
of Candida infections continues to rise, especially among
hospital patients7. For example, over a 13-year period (19801992) there was a 5-fold increase in bloodstream infections
caused by Candida in US hospitals.
To understand why this is happening, it is necessary to look at
Candida fungus in greater detail.
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Graphics by Doig Simmonds after C.C.Odds 1988
Candida in its yeast form is considered a normal gut
inhabitant when present in low numbers.
One of the reasons why C. albicans is such a persistent
pathogen is that it can take two forms. Most of the time it
exists as a single-celled yeast, but sometimes it converts to a
mycelium (a network of fine filaments). The yeast-form can
flow more easily in fluid and the mycelium-form can move
more easily between the cells of human tissues by the
insertion of growing tubes (hyphae). There is also a third and
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intermediate form, known as pseudohyphae, which are
strings of elongated yeast cells, and these structures also
appear to have invasive ability9. These different forms of the
fungus may all coexist together. The ability to change form,
which can occur quickly10, makes it easier for C. albicans to
resist the body’s various defence mechanisms.
appropriate microbial stimulation at an early age. The latest
version of the hygiene hypothesis proposes that the gut
microflora is missing certain microbes, such as helminthic
worms, that are important in an evolutionary context to the
proper development of our immune systems. If infants do
not have their gut lymphoid tissues suitably provoked by the
gut flora, their immune system may not function efficiently in
later life.
Given these potential factors behind Candida infection, it is
no surprise that a number of experts have concluded that the
most important aspect of avoiding Candida infection is
having a balanced microbial flora and a healthy immune
system2,13. This has led people to consider the use of
probiotics, because these beneficial microbes are good at
restoring disturbed microflora and improving immune
function.
Graphics by Doig Simmonds after C.C.Odds 1988
The multicelluar form of Candida albicans can make it
easier to resist the body’s defence mechanisms.
Candida infection (candidiasis) causes two main types of
disease: superficial and systemic. Superficial infection, known
as ‘thrush’, may occur in the mouth or vagina, with the
production of a white itchy surface layer, and also discharge
from the vagina5. Superficial candidiasis may also occur on
the skin, especially at moist folds and creases.
Systemic candidiasis involves the passage of Candida cells
into the bloodstream, where they may form colonies in
almost any part of the body. Such entry through the skin or
mucosal surfaces usually only occurs if there is damage to
these surfaces. Systemic candidiasis can be life-threatening
and is especially difficult to treat.
The increase in incidence of candidiasis infections is probably
due, in part, to the greater use of broad-spectrum antibiotics
that disturb the microflora. In vitro studies have shown that
colonic microflora reduces Candida spp. numbers11, and in
vivo studies have shown that the use of broad-spectrum
antibiotics increases the risk of candidal infection4,6,12.
Antibiotics kill or inhibit bacteria, but leave fungi unaffected.
With the bacteria of the gut microflora disturbed, there is
opportunity for Candida numbers to increase substantially.
Another factor in the increased incidence of Candida
infection, is the greater use of corticosteroids and other
immunosuppressive agents that alter the functioning of the
immune system13. The relevance of a weakened immune
system is reflected in the fact that leukaemia patients carry
higher levels of Candida spp.14 and patients with HIV virus are
much more likely to develop candidiasis.
The increase in Candida infections may also be due to the
‘hygiene’ effect. The hygiene hypothesis blames the increase
in diseases of the malfunctioning immune system (e.g.
asthma, eczema, autoimmune diseases) on the absence of
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Evidence of Probiotic Benefits
There have been a number of clinical studies examining the
effects of probiotics on vaginal candidiasis. A group of
women with recurrent vaginal candidiasis consumed yoghurt
containing Lactobacillus acidophilus for six months, and
there was a three-fold lower level of infections compared to
the control group15.
In a more recent randomised controlled trial (RCT), an oral
probiotic consisting of two Lactobacillus species (a
Lactobacillus rhamnosus and a Lactobacillus reuteri)
significantly improved the effectiveness of an anti-fungal
drug. Vaginal discharge was reduced, as were Candida cell
numbers16.
There have also been two studies in which the probiotics
were administered vaginally. One used a L. rhamnosus and
the other used a L. acidophilus. Both showed benefit,
including a halving of the risk of developing candidiasis in
the latter study17.
A RCT has also been undertaken with 80 premature infants,
with a view to preventing candidiasis. Candida can be a
major threat to the lives of such infants with their
underdeveloped immune systems. The group of infants
receiving L. rhamnosus for six weeks were significantly less
likely to have their intestine colonised by Candida (23%
compared with 49% in the control group)18.
Different Species
A number of different probiotic species were used in the
above studies, so how important is the type of species used
in a probiotic product? By definition, species of bacteria have
different characteristics. In fact, even within a species, some
strains behave slightly differently. Therefore it can be
expected that some probiotic bacteria will be more effective
against Candida than others.
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Furthermore, the mechanisms of benefit from probiotic
bacteria are wide-ranging. This should not be surprising,
because we are dealing with a living organism (the
bacterium) interacting with cells of another organism
(human being). Their complicated metabolisms and surface
structures are bound to offer a range of potential influences.
The importance of species used was demonstrated in one
study of mice using four different probiotic species. Two of
the species (Bifidobacterium animalis and L. acidophilus)
were superior to the other two (L. reuteri and Lactobacillus
casei) in controlling Candida19.
Conclusion
Unfortunately, good quality studies on the use of probiotics
against candidiasis are still relatively uncommon, and a clear
picture of the most desirable characteristics of a probiotic
species has not yet been obtained. Pending more research, it
may be that a good quality, multi-species probiotic is
currently the best choice.
Candida infections can occur in men as well as women.
References
1. Ruhnke M. 2002. Skin and Mucous Membrane Infections. In Candida and Candidiasis
12. Krause R, Schwab E, Bachhiesl D, et al. 2001. Role of Candida in Antibiotic-associated
(Calderone, R.A., ed.) ASM Press, Washington, D.C., U.S.A.: 307-325.
Diarrhea. The Journal of Infectious Diseases 184: 1065-1069.
2. Bernhardt H. & Knoke M. 1997. Mycological Aspects of Gastrointestinal Microflora.
13. Mitchell TG. 2004. Medical Mycology. In Jawetz, Melnick & Adelberg’s Medical
Scandinavian Journal of Gastroenterology 32 Suppl 222: 102-106.
Microbiology (Brooks GF, Butel JS & Morse SA, eds.). Lange Medical Books/McGraw-Hill, New
3. Ott SJ, Kuhbacher T, Musfeldt M, Rosenstiel P, Hellmig S, Rehman A, Drews O, Weichert W,
York, U.S.A.: 623-659.
Timmis KN, Schreiber S. 2008. Fungi and inflammatory bowel diseases: alterations of
14. Tomoda T, Nakano Y & Kageyama T. 1988. Intestinal Candida Overgrowth and Candida
composition & diversity. Scandinavian Journal of Gastroenterology 43: 831-841.
Infection in Patients with Leukemia: Effect of Bifidobacterium Administration. Bifidobacteria
4. Samonis G, Gikas A, Anaissie EJ, Vrenzos G, Maraki S, Tselentis Y, Bodey GP. 1993
and Microflora 7: 71-74.
Prospective Evaluation of Effects of Broad-Spectrum Antibiotics on Gastrointestinal Yeast
15. Hilton E, Isenberg HD, Alperstein P, France K, Borenstein MT. 1992. Ingestion of Yogurt
Colonisation of Humans. Antimicrobial Agents and Chemotherapy 37: 51-53.
Containing Lactobacillus acidophilus as Prophylaxis for Candidal Vaginitis. Annals of Internal
5. MacCallum D. 2007. Candida albicans: New Insights in Infection, Disease and Treatment.
Medicine 116: 353-357.
In New Insights in Medical Mycology (Kavanagh, K., ed.). Springer, Dordrecht, The
16. Martinez R, Franceschini S, Patta M, Quintana SM, Candido RC, Ferreira JC, De Martinis
Netherlands: 99-129.
EC, Reid G. 2009. Improved treatment of vulvovaginal candidiasis with fluconazole plus
6. Mavromanolakis E, Maraki S, Cranidis A, Tselentis Y, Kontoyiannis DP, Samonis G. 2001.
probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Letters in Applied
The Impact of Norfloxacin, Ciprofloxacin and Ofloxacin on Human Gut Colonisation by
Microbiology 48: 269-274.
Candida albicans. Scandinavian Journal of Infectious Diseases 33: 477-478.
17. Falagas ME, Betsi GI & Athanasiou S. 2006. Probiotics for prevention of recurrent
7. Lewis RE & Klepser ME. 1999. The changing face of nosocomial candidemia:
vulvovaginal candidiasis: a review. Journal of Antimocrobial Chemotherapy 58: 266-272.
Epidemiology, resistance, & drug therapy. American Journal of Health-system Pharmacy 56:
18. Manzoni P, Mastert M, Leonessa ML, Priolo C, Farina D, Monetti C, Latino MA, Gomirato
525-533.
G. 2006. Supplementation with Lactobacillus casei Subspecies rhamnosus Prevents Enteric
8. Pfaller MA & Diekema DJ. 2007. Epidemiology of invasive candidiasis: a persistent public
Colonisation by Candida Species in Pre-term Neonates: A Randomised Study. Clinical
health problem. Clinical Microbiology Reviews 20: 133-163.
Infectious Diseases 42: 1735-1742.
9. Gow NAR, Brown AJP & Odds FC. 2002. Fungal morphogenesis and host invasion. Current
19. Wagner RD, Pierson C, Warner T, Dohnalek M, Farmer J, Roberts L, Hilty M, Balish E.
Opinion in Microbiology 5: 366-371.
1997. Biotherapeutic Effects of Probiotic Bacteria on Candidiasis in Immunodeficient Mice.
10. Dignani MC, Solomkin JS & Anaissie EJ. 2003. Candida. In Clinical Mycology (Anaissie EJ,
Infection and Immunity 65: 4165-4172.
McGinnis MR & Pfaller MA, eds.). Churchill Livingstone, Philadelphia, U.S.A: 195-239.
11. Matthews HL & Witek-Janusek L. 2002. Host Defense against Oral, Esophageal, and
Gastrointestinal Candidiasis. In Candida and Candidiasis (Calderone, R.A., ed.). ASM Press,
Washington, D.C., U.S.A.: 179-192.
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About the author
Peter Cartwright MSc MA
Peter Cartwright has 17 years experience of working for patient and self-help associations, as Assistant Director of the
National Association for Colitis and Crohn’s Disease, Director of the British Stammering Association and National
Development Officer of the Self-Help Alliance. Currently he is a Trustee of the Bladder & Bowel Foundation. Peter has an
MSc in Microbiology and an MA in Sociology. He is the author of three books for the general public on intestinal health,
including Probiotics for Crohn’s and Colitis and has given over 40 lectures on probiotics to doctors in 10 countries.
Probiotics International Ltd is one of the largest manufacturers and suppliers of probiotic supplements for the healthcare,
veterinary and animal health industry. Products are marketed under the brand name of Protexin.
As published in:
2010. The Clinical Use of Probiotics. Ed Barlow J.
Probiotics International Ltd, United Kingdom.
©Probiotics International Ltd.
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